Identification of stem cell populations in sweat glands and ducts reveals roles in homeostasis and wound repair.

Sweat glands are abundant in the body and essential for thermoregulation. Like mammary glands, they originate from epidermal progenitors. However, they display few signs of cellular turnover, and whether they have stem cells and tissue-regenerative capacity remains largely unexplored. Using lineage tracing, we here identify in sweat ducts multipotent progenitors that transition to unipotency after developing the sweat gland. In characterizing four adult stem cell populations of glandular skin, we show that they display distinct regenerative capabilities and remain unipotent when healing epidermal, myoepithelial-specific, and lumenal-specific injuries. We devise purification schemes and isolate and transcriptionally profile progenitors. Exploiting molecular differences between sweat and mammary glands, we show that only some progenitors regain multipotency to produce de novo ductal and glandular structures, but that these can retain their identity even within certain foreign microenvironments. Our findings provide insight into glandular stem cells and a framework for the further study of sweat gland biology.

Agouti-Induced Anxiety-Like Behavior Is Mediated by Central Serotonergic Pathways in Zebrafish.

Overexpression of the agouti-signaling protein (asip1), an endogenous melanocortin antagonist, under the control of a constitutive promoter in zebrafish [Tg(Xla.Eef1a1:Cau.Asip1]iim4] (asip1-Tg) increases food intake by reducing sensitivity of the central satiety systems and abolish circadian activity rhythms. The phenotype also shows increased linear growth and body weight, yet no enhanced aggressiveness in dyadic fights is observed. In fact, asip1-Tg animals choose to flee to safer areas rather than face a potential threat, thus suggesting a potential anxiety-like behavior (ALB). Standard behavioral tests, i.e., the open field test (OFT), the novel object test (NOT), and the novel tank dive test (NTDT), were used to investigate thigmotaxis and ALB in male and female zebrafish. Results showed that the asip1-Tg strain exhibited severe ALB in every test, mainly characterized by pronounced freezing behavior and increased linear and angular swimming velocities. asip1-Tg animals exhibited low central serotonin (5-HT) and dopamine (DA) levels and high turnover rates, thus suggesting that central monoaminergic pathways might mediate melanocortin antagonist-induced ALB. Accordingly, the treatment of asip1-Tg animals with fluoxetine, a selective serotonin reuptake inhibitor (SSRI), reversed the ALB phenotype in NTDT as well as 5-HT turnover. Genomic and anatomical data further supported neuronal interaction between melanocortinergic and serotonergic systems. These results suggest that inhibition of the melanocortin system by ubiquitous overexpression of endogenous antagonist has an anxiogenic effect mediated by serotonergic transmission.

Disturbed flow increases endothelial inflammation and permeability via a Frizzled-4-ß-catenin-dependent pathway.

Multidirectional or disturbed flow promotes endothelial dysfunction and is associated with early atherogenesis. Here we investigated the role of Wnt signalling in flow-mediated endothelial dysfunction. The expression of Frizzled-4 was higher in cultured human aortic endothelial cells (ECs) exposed to disturbed flow compared to that seen for undisturbed flow, obtained using an orbital shaker. Increased expression was also detected in regions of the porcine aortic arch exposed to disturbed flow. The increased Frizzled-4 expression in cultured ECs was abrogated following knockdown of R-spondin-3. Disturbed flow also increased the nuclear localisation and activation of ß-catenin, an effect that was dependent on Frizzled-4 and R-spondin-3. Inhibition of ß-catenin using the small-molecule inhibitor iCRT5 or knockdown of Frizzled-4 or R-spondin-3 resulted in reduced expression of pro-inflammatory genes in ECs exposed to disturbed flow, as did inhibition of WNT5A signalling. Inhibition of the canonical Wnt pathway had no effect. Inhibition of ß-catenin also reduced endothelial paracellular permeability; this was associated with altered junctional and focal adhesion organisation and cytoskeletal remodelling. These data suggest the presence of an atypical Frizzled-4-ß-catenin pathway that promotes endothelial dysfunction in response to disturbed flow.

Açaí (Euterpe oleracea Mart.) Seed Oil and Its Nanoemulsion: Chemical Characterisation, Toxicity Evaluation, Antioxidant and Anticancer Activities.

This study explores a nanoemulsion formulated with açaí seed oil, known for its rich fatty acid composition and diverse biological activities. This study aimed to characterise a nanoemulsion formulated with açaí seed oil and explore its cytotoxic effects on HeLa and SiHa cervical cancer cell lines, alongside assessing its antioxidant and toxicity properties both in vitro and in vivo. Extracted from fruits sourced in Brazil, the oil underwent thorough chemical characterization using gas chromatography-mass spectrometry. The resulting nanoemulsion was prepared and evaluated for stability, particle size, and antioxidant properties. The nanoemulsion exhibited translucency, fluidity, and stability post centrifugation and temperature tests, with a droplet size of 238.37, PDI -9.59, pH 7, and turbidity 0.267. In vitro assessments on cervical cancer cell lines revealed antitumour effects, including inhibition of cell proliferation, migration, and colony formation. Toxicity tests conducted in cell cultures and female Swiss mice demonstrated no adverse effects of both açaí seed oil and nanoemulsion. Overall, açaí seed oil, particularly when formulated into a nanoemulsion, presents potential for cancer treatment due to its bioactive properties and safety profile.

Mismatch novelty exploration training shifts VPAC1 receptor-mediated modulation of hippocampal synaptic plasticity by endogenous VIP in male rats.

Novelty influences hippocampal-dependent memory through metaplasticity. Mismatch novelty detection activates the human hippocampal CA1 area and enhances rat hippocampal-dependent learning and exploration. Remarkably, mismatch novelty training (NT) also enhances rodent hippocampal synaptic plasticity while inhibition of VIP interneurons promotes rodent exploration. Since VIP, acting on VPAC1 receptors (Rs), restrains hippocampal LTP and depotentiation by modulating disinhibition, we now investigated the impact of NT on VPAC1 modulation of hippocampal synaptic plasticity in male Wistar rats. NT enhanced both CA1 hippocampal LTP and depotentiation unlike exploring an empty holeboard (HT) or a fixed configuration of objects (FT). Blocking VIP VPAC1Rs with PG 97269 (100 nM) enhanced both LTP and depotentiation in naïve animals, but this effect was less effective in NT rats. Altered endogenous VIP modulation of LTP was absent in animals exposed to the empty environment (HT). HT and FT animals showed mildly enhanced synaptic VPAC1R levels, but neither VIP nor VPAC1R levels were altered in NT animals. Conversely, NT enhanced the GluA1/GluA2 AMPAR ratio and gephyrin synaptic content but not PSD-95 excitatory synaptic marker. In conclusion, NT influences hippocampal synaptic plasticity by reshaping brain circuits modulating disinhibition and its control by VIP-expressing hippocampal interneurons while upregulation of VIP VPAC1Rs is associated with the maintenance of VIP control of LTP in FT and HT animals. This suggests VIP receptor ligands may be relevant to co-adjuvate cognitive recovery therapies in aging or epilepsy, where LTP/LTD imbalance occurs.

Testing phylogenetic signal with categorical traits and tree uncertainty.

SUMMARY: The phylogenetic signal, frequently used to identify signatures of adaptive evolution or important associations between genes and phenotypes, measures the tendency for recently diverged species to resemble each other more than distantly related species. An example of such a measure is the δ statistic, which uses Shannon entropy to measure the degree of phylogenetic signal between a categorical trait and a phylogeny. In this study, we refined this statistic to account for tree uncertainty, resulting in more accurate assessments of phylogenetic associations. In addition, we provided a more accessible and computationally efficient implementation of the δ statistic that will facilitate its use by the evolutionary community. AVAILABILITY AND IMPLEMENTATION: github.com/diogo-s-ribeiro/delta-statistic.

Prevalence and Trajectories of Post-COVID-19 Neurological Manifestations: A Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points. METHODS: The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times. RESULTS: 126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence. DISCUSSION: Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.

Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial.

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

CENTRAL AND PERIPHERAL INVOLVEMENT OF THE RETINA IN THE INITIAL STAGES OF DIABETIC RETINOPATHY.

PURPOSE: To determine the degree of central microvascular closure using optical coherence tomography angiography in eyes of patients with type 2 diabetes with visible lesions only in the central retina or only in the periphery. METHODS: Cross-sectional study. All 127 eyes underwent ultra-widefield fundus photography 200° examinations with OPTOS California (Optos, Dunfermline, United Kingdom) and Cirrus Angioplex optical coherence tomography angiography 3 × 3 mm acquisitions (ZEISS, Dublin, CA). RESULTS: Twenty-five eyes showed visible lesions only in the central retina, 57 only in the peripheral retina, and 45 presented visible lesions in entire retina. The group with visible lesions only in the periphery showed definite closure in the superficial capillary plexus in 49% of the eyes, whereas the group with visible lesions only in the central seven-early treatment diabetic retinopathy study fields area showed a definite closure in 64%. CONCLUSION: Central capillary closure is already present in the initial stages of diabetic retinopathy even when lesions are only visible in the peripheral retina. Capillary closure in the superficial capillary plexus is three times more frequent than in the deep capillary plexus, demonstrating earlier closure of the superficial capillary plexus. Eyes with visible lesions only in the periphery show a milder form of retinopathy.

ETDRS grading with CLARUS ultra-widefield images shows agreement with 7-fields colour fundus photography.

BACKGROUND: To analyse and compare the grading of diabetic retinopathy (DR) severity level using standard 35° ETDRS 7-fields photography and CLARUS™ 500 ultra-widefield imaging system. METHODS: A cross-sectional analysis of retinal images of patients with type 2 diabetes (n = 160 eyes) was performed for this study. All patients underwent 7-fields colour fundus photography (CFP) at 35° on a standard Topcon TRC-50DX® camera, and ultra-widefield (UWF) imaging at 200° on a CLARUS™ 500 (ZEISS, Dublin, CA, USA) by an automatic montage of two 133° images (nasal and temporal). 35° 7-fields photographs were graded by two graders, according to the Early Treatment Diabetic Retinopathy Study (ETDRS). For CLARUS UWF images, a prototype 7-fields grid was applied using the CLARUS review software, and the same ETDRS grading procedures were performed inside that area only. Grading of DR severity level was compared between these two methods to evaluate the agreement between both imaging techniques. RESULTS: Images of 160 eyes from 83 diabetic patients were considered for analysis. According to the 35° ETDRS 7-fields images, 22 eyes were evaluated as DR severity level 10-20, 64 eyes were evaluated as DR level 35, 41 eyes level 43, 21 eyes level 47, 7 eyes level 53, and 5 eyes level 61. The same DR severity level was achieved with CLARUS 500 UWF images in 92 eyes (57%), showing a perfect agreement (k > 0.80) with the 7-fields 35° technique. Fifty-seven eyes (36%) showed a higher DR level with CLARUS UWF images, mostly due to a better visualization of haemorrhages and a higher detection rate of intraretinal microvascular abnormalities (IRMA). Only 11 eyes (7%) showed a lower severity level with the CLARUS UWF system, due to the presence of artifacts or media opacities that precluded the correct evaluation of DR lesions. CONCLUSIONS: UWF CLARUS 500 device showed nearly perfect agreement with standard 35° 7-fields images in all ETDRS severity levels. Moreover, CLARUS images showed an increased ability to detect haemorrhages and IRMA helping with finer evaluation of lesions, thus demonstrating that a UWF photograph can be used to grade ETDRS severity level with a better visualization than the standard 7-fields images. TRIAL REGISTRATION: Approved by the AIBILI - Association for Innovation and Biomedical Research on Light and Image Ethics Committee for Health with number CEC/009/17- EYEMARKER.

The role of the visceral adiposity index in the assessment of metabolic syndrome of polycystic ovary syndrome patients: a new anthropometric index.

PURPOSE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder often linked to metabolic syndrome (MS), raising the risk of cardiovascular disease and type II diabetes. Certain indicators, such as the lipid accumulation product (LAP) and homeostatic model assessment for insulin resistance (HOMA-IR), can predict MS in PCOS patients. This study aimed to assess the predictive power of the visceral adiposity index (VAI) in comparison to LAP and HOMA-IR as predictors of MS in PCOS patients. METHODS: In this cross-sectional observational study, data from 317 diagnosed PCOS women were analyzed. VAI, LAP, and HOMA-IR were computed as indexes. Participants were categorized into two groups for index accuracy comparison: PCOS patients with and without MS. The data were assessed using a ROC curve. RESULTS: Among PCOS women with MS, 92.3% had abnormal VAI results, 94.5% had abnormal LAP results, and only 50.5% had abnormal HOMA-IR results. Conversely, the majority of PCOS women without MS had normal HOMA-IR (64.6%). When comparing these indexes using the ROC curve, VAI displayed the highest accuracy, followed by LAP and HOMA-IR. CONCLUSION: The VAI index proved to be a superior predictor of metabolic MS in PCOS women when compared to other indexes.

Integrating sEMG and IMU Sensors in an e-Textile Smart Vest for Forward Posture Monitoring: First Steps.

Currently, the market for wearable devices is expanding, with a growing trend towards the use of these devices for continuous-monitoring applications. Among these, real-time posture monitoring and assessment stands out as a crucial application given the rising prevalence of conditions like forward head posture (FHP). This paper proposes a wearable device that combines the acquisition of electromyographic signals from the cervical region with inertial data from inertial measurement units (IMUs) to assess the occurrence of FHP. To improve electronics integration and wearability, e-textiles are explored for the development of surface electrodes and conductive tracks that connect the different electronic modules. Tensile strength and abrasion tests of 22 samples consisting of textile electrodes and conductive tracks produced with three fiber types (two from Shieldex and one from Imbut) were conducted. Imbut's Elitex fiber outperformed Shieldex's fibers in both tests. The developed surface electromyography (sEMG) acquisition hardware and textile electrodes were also tested and benchmarked against an electromyography (EMG) gold standard in dynamic and isometric conditions, with results showing slightly better root mean square error (RMSE) values (for 4 × 2 textile electrodes (10.02%) in comparison to commercial Ag/AgCl electrodes (11.11%). The posture monitoring module was also validated in terms of joint angle estimation and presented an overall error of 4.77° for a controlled angular velocity of 40°/s as benchmarked against a UR10 robotic arm.

The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3.

Adrenal glands are zonated endocrine organs that are essential in controlling body homeostasis. How zonation is induced and maintained and how renewal of the adrenal cortex is ensured remain a mystery. Here we show that capsular RSPO3 signals to the underlying steroidogenic compartment to induce ß-catenin signaling and imprint glomerulosa cell fate. Deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth. Importantly, Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa. Thus, the adrenal capsule acts as a central signaling center that ensures replacement of damaged cells and is required to maintain zonation throughout life.

Harvesting the Power of Green Synthesis: Gold Nanoparticles Tailored for Prostate Cancer Therapy.

Biosynthetic gold nanoparticles (bAuNPs) present a promising avenue for enhancing bio-compatibility and offering an economically and environmentally responsible alternative to traditional production methods, achieved through a reduction in the use of hazardous chemicals. While the potential of bAuNPs as anticancer agents has been explored, there is a limited body of research focusing on the crucial physicochemical conditions influencing bAuNP production. In this study, we aim to identify the optimal growth phase of Pseudomonas aeruginosa cultures that maximizes the redox potential and coordinates the formation of bAuNPs with increased efficiency. The investigation employs 2,6-dichlorophenolindophenol (DCIP) as a redox indicator. Simultaneously, we explore the impact of temperature, pH, and incubation duration on the biosynthesis of bAuNPs, with a specific emphasis on their potential application as antitumor agents. Characterization of the resulting bAuNPs is conducted using ATR-FT-IR, TEM, and UV-Vis spectroscopy. To gain insights into the anticancer potential of bAuNPs, an experimental model is employed, utilizing both non-neoplastic (HPEpiC) and neoplastic (PC3) epithelial cell lines. Notably, P. aeruginosa cultures at 9 h/OD600 = 1, combined with biosynthesis at pH 9.0 for 24 h at 58 °C, produce bAuNPs that exhibit smaller, more spherical, and less aggregated characteristics. Crucially, these nanoparticles demonstrate negligible effects on HPEpiC cells while significantly impacting PC3 cells, resulting in reduced viability, migration, and lower IL-6 levels. This research lays the groundwork for the development of more specialized, economical, and ecologically friendly treatment modalities.

The impact of using the levonorgestrel-releasing intrauterine device on the incidence of acne in adolescents and young women.

PURPOSE: To evaluate the impact of levonorgestrel-releasing intrauterine device (LNG-IUD) use on the incidence of acne in adolescents and young women. METHODS: A narrative review was conducted in PubMed, Embase, Cochrane, and SciELO assessing the incidence of acne in adolescents and young women using LNG-IUD (13.5, or 19.5 mg, or 52 mg). Cohort, cross-sectional studies, clinical trials, and meta-analyses were included, without a date limit. Studies that didn't evaluate women in the age of interest were excluded. Only articles in English were selected. RESULTS: Nine articles were included in this narrative review. Only clinical trials, cohort studies, and cross-sectional studies were evaluated. Two cross-sectional studies evaluated the incidence of acne in women using any contraceptive methods, with the incidence of acne being 36% in women aged 17 to 47 using LNG-IUD in one study. In another study, acne incidence ranged from 2 to 8% in women using any contraceptive methods, with higher rates in younger women and LNG-IUD users. The incidence of acne varies and participants between 16 to 35 years were more likely to report new acne or worsening of pre-existing acne. In a prospective cohort study of women between 16 and 24 years, acne was a common adverse effect, with 44% in the first year. CONCLUSION: The data indicate variability in the incidence of acne among LNG-IUD users, with a higher prevalence observed in younger women. Further research should focus on the effects of LNG-IUD on acne in young populations, with rigorous study designs and consideration of previous contraceptive use.

The levonorgestrel-releasing intrauterine device (LNG-IUD) is an important tool in the prevention of unplanned pregnancies in adolescents and young women. Acne is a possible adverse effect that could lead to discontinuation of the method.

MEDICAL-SURGICAL MANAGEMENT OF INTESTINAL INFECTION BY PROSTHENORCHIS ELEGANS IN NONHUMAN PRIMATES FROM COSTA RICA.

Parasitism is one of the most important diseases in nonhuman primates (NHP). Parasitism by Prosthenorchis elegans can be a threat to health and conservation of NHP in Costa Rica. Surgical management of intestinal acanthocephalan infection in two squirrel monkeys (Saimiri oerstedii) and one white-faced monkey (Cebus imitator) is described as an alternative to the lack of pharmacologic control options when there is a high burden of parasites present. A complete physical evaluation, including medical ultrasound techniques, allow for diagnosis of the parasite and its lesions. When animals present with a high burden of parasites, surgical management has shown to promote good health outcomes and increase the probability of survival.

Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration.

BACKGROUND & AIMS: Mouse models of lineage tracing have helped to describe the important subpopulations of hepatocytes responsible for liver regeneration. However, conflicting results have been obtained from different models. Herein, we aimed to reconcile these conflicting reports by repeating a key lineage-tracing study from pericentral hepatocytes and characterising this Axin2CreERT2 model in detail. METHODS: We performed detailed characterisation of the labelled population in the Axin2CreERT2 model. We lineage traced this cell population, quantifying the labelled population over 1 year and performed in-depth phenotypic comparisons, including transcriptomics, metabolomics and analysis of proteins through immunohistochemistry, of Axin2CreERT2 mice to WT counterparts. RESULTS: We found that after careful definition of a baseline population, there are marked differences in labelling between male and female mice. Upon induced lineage tracing there was no expansion of the labelled hepatocyte population in Axin2CreERT2 mice. We found substantial evidence of disrupted homeostasis in Axin2CreERT2 mice. Offspring are born with sub-Mendelian ratios and adult mice have perturbations of hepatic Wnt/ß-catenin signalling and related metabolomic disturbance. CONCLUSIONS: We find no evidence of predominant expansion of the pericentral hepatocyte population during liver homeostatic regeneration. Our data highlight the importance of detailed preclinical model characterisation and the pitfalls which may occur when comparing across sexes and backgrounds of mice and the effects of genetic insertion into native loci. IMPACT AND IMPLICATIONS: Understanding the source of cells which regenerate the liver is crucial to harness their potential to regrow injured livers. Herein, we show that cells which were previously thought to repopulate the liver play only a limited role in physiological regeneration. Our data helps to reconcile differing conclusions drawn from results from a number of prior studies and highlights methodological challenges which are relevant to preclinical models more generally.

Changes in cerebral autoregulation and vasoreactivity after surgical aortic valve replacement: a prospective study.

NEW FINDINGS: What is the central question of this study? How are dynamic cerebral autoregulation and brain vasoreactivity influenced by severe aortic stenosis and its surgical treatment? What are the main findings and their importance? Dynamic cerebral autoregulation is preserved in the long term in patients with severe aortic stenosis and does not change after surgical aortic valve replacement. However, carbon dioxide vasoreactivity is impaired in these patients. ABSTRACT: Surgical aortic valve replacement (SAVR) alters the natural course of severe aortic stenosis (AS). In this study, we aimed to determine the effects of the disease on dynamic cerebral autoregulation and vasoreactivity (VR) and to assess their changes after SAVR. We recruited 23 patients diagnosed with severe AS eligible for SAVR and 15 healthy matched controls. AS patients had lower mean VR to CO2 (P = 0.005) than controls, but dynamic cerebral autoregulation was preserved. Cerebral haemodynamics showed no significant change after SAVR. Patients with smaller baseline aortic valve areas presented with smaller low frequency phase changes after surgery (P = 0.016). Severe AS does not seem to impact dynamic cerebral autoregulation but does reduce VR to CO2 . SAVR does not alter cerebral autoregulation nor vasoreactivity.

Pelvic floor dysfunctions in women with systemic lupus erythematosus: A cross-sectional study.

INTRODUCTION AND HYPOTHESIS: As a result of the impairment of the musculoskeletal system, the pelvic floor muscles are likely compromised in women with systemic lupus erythematosus (SLE). We hypothesized that women with SLE would report more symptoms of pelvic floor dysfunction (PFD) and there will be an association between SLE and PFD. METHODS: An online cross-sectional survey was conducted. Data were collected on demographic and anthropometric characteristics, PFD (urinary incontinence, nocturia, anal incontinence, genital-pelvic pain/penetration disorder and pelvic organ prolapse) and obstetric history using a web-based questionnaire. The groups were compared using the Mann-Whitney test for quantitative variables and the chi-squared test for categorical variables. The association between SLE and PFD was tested using logistic regression analysis. RESULTS: A total of 196 women answered the questionnaire (102 with SLE and 94 healthy controls). Women with SLE reported significantly more urinary incontinence, nocturia, anal incontinence, pelvic organ prolapse and genital-pelvic pain/penetration disorder than the healthy controls (p ≤ 0.05). Women with SLE were 2.8- to 3.0-fold more likely to report genital-pelvic pain/penetration disorder than healthy women. CONCLUSIONS: The prevalence of PFD was significantly higher in women with SLE compared to healthy women. Thus, PFD seems to be an important problem in women with this disease. An in-depth investigation of these disorders could contribute to the understanding of how SLE impacts pelvic floor function.

The prognostic value of delta-lactate in critically ill children.

AIM: This study aimed to test delta-lactate (ΔL) as a short-term risk stratification method in critically ill children. METHODS: An exploratory study of patients admitted to paediatric intensive care unit (PICU) was conducted. ΔL was calculated as the difference between the maximum lactate concentrations on Days 1 and 2. According to the ΔL cutoff, two groups were considered: low mortality risk (LMR) - ΔL ≥ 0.05 mmol/L - and high mortality risk (HMR) - ΔL < 0.05 mmol/L. RESULTS: Mortality, both during PICU stay and at 28 days, was statistically associated with elevated serum lactate on D1 and D2, per se. For the 93 cases with elevated lactate on Day 1, and a ΔL cutoff of 0.05 mmol/L, the area under the ROC curve was 0.698 (95% confidence interval, 0.47-0.93). HMR patients scored higher PIM3, were not discharged home until 28 days, counted fewer ventilation-free days and needed renal replacement therapy more often. CONCLUSION: Elevated lactate levels at admission, as well as applying the optimal cutoff for ΔL, allowed to predict short-term mortality: if an increase or minimal decrease in lactate maximum levels occurred from D1 to D2, death was almost eight times more probable. In critically ill children, delta-lactate predicts short-term outcome.